The present invention relates to terahertz time domain and frequency domain spectroscopy using dendrimer based terahertz sources.
The recently accessible terahertz (THz) portion of the electromagnetic spectra, also known as T-ray spectra, has a wide potential to be employed in important fundamental research, medical, biomedical, and biological studies. When converted to other units, 1 THz is equivalent to 33.33 cm−1 (wave numbers), 0.004 eV photon energy, or 300 μm wavelength. THz spectroscopy covers the region of electromagnetic spectrum from 0.3 THz to ˜20 THz (from 10 to 600 cm−1), with most of the work being done between 0.5 and ˜3 THz range.
While Fourier-transform infrared (FT-IR) spectroscopy can monitor alterations at individual bonds even in some protein complexes, thus allow monitoring structural and conformational changes in the course of a biological reaction, yet, presently available frequency range of FT-IR techniques, typically 4000-400 cm−1 (˜120-12 THz) does by far not cover the full range of functionally relevant modes of enzymes and proteins, which may extend down to 10 cm−1 (0.3 THz). This can only be done with THz spectroscopy.
To understand the interaction of far-infrared (FIR) and THz radiation with biological systems on a molecular level, i.e. on the basis of resonant processes with electronic, vibrational, and rotational states of complex biological molecules in relation to a modulation of their biological activity, which can be stimulation, inhibition, and in the worst case damage, the functionally relevant states are probed by near- and mid-infrared spectroscopy (6000 cm−1−500 cm−1), e.g., absorbance and reaction-induced difference spectra of structurally and functionally intact biological samples of proteins and enzymes. However, because many important biological events, as mentioned above, occur in the THz range, information obtained via FT-IR is not complete or sometimes insufficient. Thus, THz spectroscopy is an important tool to aid in the understanding of many crucial biological activities. Also, THz spectroscopy can uniquely discern between molecular polymorphs, hybridized and denatured DNAs, and other bio-molecular complexes of interest that can not be done with other methods such as FT-IR.
Techniques such as X-ray crystallography, 2-D NMR spectroscopy, and high-resolution electron microscopy deliver static, frozen-in-time pictures of proteins, enzymes, and biological membranes as opposed to real time live image obtainable by T-rays.
Information on the function and how it is related to the structure, requires spectroscopic techniques which probe structural properties and allow high temporal resolution on the order of pico seconds. This can not be obtained by anything other than T-ray spectroscopy.
Among the variety of spectroscopic techniques, Infrared (IR) spectroscopy has probably the best access to minute structural details, in the order of fractions of a bond dimension. Infrared spectroscopy has greatly advanced sensitivity and rapid data acquisition capabilities provided by Fourier-Transform infrared (FT-IR) spectrometers. This is still not comparable with the capabilities of T-ray spectra, because of the lack of high resolution temporal information.
These existing and promising THz applications have brought upon challenges for spectroscopy techniques as well as THz emitters and sensors. For spectroscopic applications, efficient and broadband THz radiation is necessary. Also sensitive and broad frequency response THz sensors are critical for some spectroscopy techniques.
THz emission by the electro-optic rectification (EOR) effect of electro-optic (EO) materials and THz detection by EO sampling is one method for obtaining ultra-broadband THz field. The key parts of this all-optical high resolution THz spectroscopy are to deploy high EO efficiency materials for terahertz generation and an ultra-short laser pulse source to activate the EOR effect. A second approach is to use difference frequency generation (DFG), where, a pair of lasers can be used to excite the rectification effect in an EO material. This is also known as difference frequency mixing (DFM), because, here the generated terahertz radiation wavelength falls in the region which is equal to the difference of the two pump lasers. The lasers can be pulsed to produce a pulsed THz output or CW that produces CW T-rays.